Journal of the American Chemical Society
Page 4 of 5
Dr. George Dubay for high-resolution mass spectrometry
and thank Dr. Roger Sommer for X-ray structural analysis.
Finally, we demonstrated the potential of this electro-
philic amination strategy for the intermolecular amino
oxygenation of alkenes 9 using carboxylic acids 8 and
O-benzoylhydroxylamines 2 (Scheme 4). In this three-
component version, 1,2-amino alcohols 10a–10b, result-
ing from different carboxylic acids, were readily ob-
tained under optimized conditions.14 Simiarly, 10c and
10d, with either an electron-rich or electron-deficient
group on styrenes, as well as N-Boc-piperazine 10e de-
rived from a different amino precursor all formed effi-
ciently. The remarkably higher efficacy observed on
electron-rich styrenes is consistant with the proposed
pathways for amino lactonization in Scheme 3, due to
the involvement of more stable radical intermediates.
These results also suggest the potential of O-
benzoylhydroxylamine for a new alkene difunctionaliza-
tion strategy incorporating diverse external nucleophiles.
1
2
3
4
5
6
7
8
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Scheme 4. Three-Component Intermolecular Amino Oxy-
genation of Styrenes.a
O
R1
O
R1
NR2R3
O
NR2R3
Cu(OAc)2 (20 mol%)
DCE, 80 °C, 1 h
+
+
OH
BzO
Ar
Ar
8
9
2
10
O
O
NBoc
O
O
O
O
N
O
N
O
N
(3,5-NO2)C6H3
R1
(3,5-NO2)C6H3
OMe
OMe
R
10a R1 = (3,5-NO2)C6H3 (98%)
10b R1 = Ph (59%)
10c R = 4-OMe (86%)
10d R = 4-Cl (49%)
10e (93%)
aConditions: 8 (3.0 equiv), 9 (3.0 equiv), 2 (0.4 mmol, 1.0
equiv), Cu(OAc)2 (20 mol%), DCE (2.0 mL), 80 oC, 1 h.
In summary, we have developed a copper-catalyzed
amino lactonization of unsaturated carboxylic acids as
well as the three-component intermolecular amino oxy-
genation of alkenes using O-benzoylhydroxylamines as
an electrophilic amination agent. This transformation
offers a unique and efficient approach to directly access
a wide range of amino γ- and δ-lactones as well as 1,2-
amino alcohol derivatives that are of great value in or-
ganic synthesis and medicine.
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S. M. S.; Aziz, S. M. Chem. Commun. 2014, 50, 6913.
ASSOCIATED CONTENT
Supporting Information
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The Supporting Information is available free of charge on
the ACS Publications website. Experimental procedures,
additional screening data, characterization data including
NMR spectra, and crystallographic data for 3r’.
AUTHOR INFORMATION
Corresponding Author
E-mail: qiu.wang@duke.edu
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(10) See more details in the Supporting Information.
ACKNOWLEDGMENT
We acknowledge financial support by Duke University and
the Burroughs Wellcome fellowship (B.N.H). We thank
ACS Paragon Plus Environment